Ketoconazole

Ketoconazole is an azole medication used to treat a broad spectrum of fungi It was originally developed in the late 1970's in the oral form and granted FDA acceptance in 1981. Shortly after the topical formulations were undergoing trials and proven effective. The 2% cream and 1% shampoo are now available over the counter. It is effective against yeasts and dermatophytes, both systemically and topically. It is now mainly used systemically in treating life-threatening fungal infections

Other effects may include headache, dizziness and drowsiness. Azospermia, impotence, decreased libido in menstrual irregularities may occur as a result of corticosteroid and testosterone suppression.

FDA Pregnancy Category CAnimal studies have shown teratogenicity and embryonic toxicity when given very high oral doses. Use of ketoconazole is not recommended during pregnancy or lactation.

Mechanism of Action / Pharmacokinetics

The azole antifungals interfere with cytochome P450 enzyme activity and inhibit demethylization of 14-alpha-methylsterolsterols to ergosterol. Since ergosterol is essential to the fungal cell membrane, when it is depleted the fungal cells are destroyed.Ketoconazole may also interfere with the conversion of lanosterol to cholesterol, affecting steroid hormone synthesis. Systemic ketoconazole is well distributed, however it does not penetrate the CSF. Topical application does not result in significant systemic absorption.